The present invention relates to improved aerosolizing devices, particularly but not exclusively for atomizing liquid medicaments to be inhaled, and to a method of constructing such devices.
A wide variety of procedures have been proposed to deliver a drug to a patient. Of particular interest to the present invention are drug delivery procedures where the drug is a liquid and is dispensed in the form of fine liquid droplets for inhalation by a patient. A variety of devices have been proposed for forming the dispersion, including air jet nebulizers, ultrasonic nebulizers and metered dose inhalers (MDIs). Air jet nebulizers usually utilize a high pressure air compressor and a baffle system that separates the large particles from the spray. Ultrasonic nebulizers generate ultrasonic waves with an oscillating piezoelectric crystal to produce liquid droplets. Another type of ultrasonic nebulizer is described in U.S. Pat. Nos. 5,261,601 and 4,533,082. Typical MDIs usually employ a gas propellant, such as a CFC, which carries the therapeutic substance and is sprayed into the mouth of the patient.
The present applicant has also proposed a variety of aerosolization devices for atomizing liquid solutions. For example, one exemplary atomization apparatus is described in U.S. Pat. No. 5,164,740, the complete disclosure of which is herein incorporated by reference. The atomization apparatus comprises an ultrasonic transducer and an aperture plate attached to the transducer. The aperture plate includes tapered apertures which are employed to produce small liquid droplets. The transducer vibrates the plate at relatively high frequencies so that when the liquid is placed in contact with the rear surface of the aperture plate and the plate is vibrated, liquid droplets will be ejected through the apertures. The apparatus described in U.S. Pat. No. 5,164,740 has been instrumental in producing small liquid droplets without the need for placing a fluidic chamber in contact with the aperture plate. Instead, small volumes of liquid are delivered to the rear surface of the aperture plate and held in place by surface tension forces.
Modified atomization apparatus are described in U.S. Pat. Nos. 5,586,550 and 5,758,637, the complete disclosures of which are herein incorporated by reference. The two references describe a liquid droplet generator which is particularly useful in producing a high flow of droplets in a narrow size distribution. As described in U.S. Pat. No. 5,586,550, the use of a dome shaped aperture plate is advantageous in allowing more of the apertures to eject liquid droplets.
One requirement of such aerosolization devices is the need to supply liquid to the aperture plate. In some applications, such as when delivering aerosolized medicaments to the lungs, it may be desirable to regulate the supply of the liquid to the aperture plate so that proper pulmonary delivery of the drug may occur. For example, if too much liquid is supplied, the aerosol generator may be unable to aerosolize fully all of the delivered liquid. On the other hand, if too little liquid is supplied, the user may not receive a sufficient dosage. Further, a metering process may be needed to ensure that a unit dosage amount of the liquid is delivered to the aerosol generator. This may be challenging if the user requires several inhalations in order to inhale the unit dose amount.
The present invention is related to liquid feed systems and methods for delivering liquids to the aerosol generator to facilitate aerosolization of the liquid.
The invention provides exemplary aerosolization devices and methods for aerosolizing liquids. In one embodiment, an aerosolization device comprises a liquid supply system that is adapted to hold a supply of liquid, and an aerosol generator that is configured to aerosolize liquid supplied from the liquid supply system. In one aspect, the aerosol generator may comprise a plate having a plurality of apertures and a vibratable element disposed to vibrate the plate. The aerosolization device further comprises a sensor configured to sense an amount of unaerosolized liquid supplied to the aerosol generator, and a controller to control operation of the liquid supply system based on information received from the sensor. In this way, during aerosolization the amount of unaerosolized liquid supplied to the aerosol generator remains within a certain range. In this manner, the device is configured to prevent either too much or too little liquid from being supplied to the aerosol generator at any one time.
In one aspect, the sensor comprises a strain gauge coupled to the aerosol generator for detecting variations in strain caused by varying amounts of unaerosolized liquid adhering to the aerosol generator. The strain gauge may comprise a piezoelectric element coupled to the aerosol generator such that variations in an electrical characteristic (e.g. impedance) are representative of unaerosolized liquid adhering to the aerosol generator. The piezoelectric element may also act as a transducer disposed to vibrate an aperture plate in the aerosol generator.
In another aspect, the sensor may comprise an optical sensor. The optical sensor may be configured to sense the presence or absence of unaerosolized liquid at a certain location on the aerosol generator. The certain location may be spaced from where liquid is supplied to the aerosol generator.
In yet another aspect, the sensor may be a conductivity sensor that is configured to sense electrical conductivity between at least two points across a surface of the aerosol generator on which unaerosolized liquid may adhere. At least one of the points may be spaced from where liquid is supplied to the aerosol generator. Further, at least one of the points may be closer to where liquid is supplied to the aerosol generator than another one of the points. In this way, sensing electrical conductivity may give an indication of unaerosolized liquid distribution across the aerosol generator.
In one particular embodiment, the amount of unaerosolized liquid on the aerosol generator remains within the range from about 0 to about 20 microliters, and more preferably from about 2 microliters to about 20 microliters.
The device may further comprise a housing having a mouthpiece, with the aerosol generator disposed in the housing for delivery of aerosolized liquid through the mouthpiece. In this way, a drug may be aerosolized and ready for pulmonary delivery upon patient inhalation.
In another particular aspect, the liquid supply system may comprise a dispenser for dispensing a certain amount of liquid upon receipt of an appropriate signal from the controller. In this way, a predetermined amount of liquid may be chosen to ensure the aerosol generator is not overloaded at any one time. The device may further comprise a meter for limiting the number of times the dispenser is activated during operation of the aerosol generator. In this way, the total liquid delivered by the aerosol generator in any one period of operation may be accurately controlled, thereby limiting the risk of delivering below or above a recommended dose.
In yet another particular embodiment, the device may further comprise a heater for heating unaerosolized liquid supplied to the aerosol generator. The heater may be adapted to heat the aerosol generator to vaporize or burn off residual unaerosolized liquid after aerosol generator cessation. In this way, residual unaerosolized liquid may be removed to prevent interference with a subsequent aerosolization event. The heater may comprise an electrical resistance heater and an electrical power supply (e.g. battery) for energizing resistance heating.
In another embodiment of the invention, a method for aerosolizing a liquid utilizes an aerosol generator that is operable to aerosolize a liquid. According to the method, a liquid is supplied to the aerosol generator from a liquid supply system at an initial flow rate. During aerosolization, the amount of supplied liquid remaining unaerosolized is sensed and the rate of liquid supply regulated based upon the sensed amount. The rate of liquid supply may be decreased if the sensed amount exceeds a certain value, and the rate of liquid supply may be increased if the sensed amount falls below a critical level. In this way, it is possible to prevent or to reduce the extent of supplying too much or too little liquid being supplied to the aerosol generator at any one time.
In one aspect, the method further comprises providing a heater for heating unaerosolized liquid supplied to the aerosol generator. By sensing whether any of the supplied liquid remains unaerosolized after cessation of the liquid supply, the heater may be operated to vaporize or burn-off such supplied liquid remaining on the aerosol generator.
In yet another embodiment of the invention, an aerosolization device comprises a liquid supply system that is adapted to hold a supply of liquid, and an aerosol generator comprising a plate having a plurality of apertures and an electric transducer disposed to vibrate the plate when energized. A sensor is configured to sense an electrical characteristic of the electrical transducer that is dependent upon an amount of unaerosolized liquid adhering to the plate. A controller is provided to regulate operation of the liquid supply in order to maintain the amount of unaerosolized liquid adhering to the plate within a certain range during aerosolization.
In a still further embodiment, a method is provided for controlling the supply of a liquid to an aerosol generator. According to the method, a liquid supply system is operated to supply a liquid to a vibratable aperture plate of an aerosol generator. An amount of liquid adhering to the vibratable plate is sensed and is used to control the amount of liquid supplied to the plate. By controlling operation of the liquid supply system, the amount of liquid adhering to the vibratable aperture plate may be regulated.